The murine Ly-6 locus encodes a group of cell surface molecules expressed on a variety of lymphoid, myeloid and other cell types. At least two of these Ly-6 encoded molecules, Ly-6E.1 and TAP, and involved in T lymphocytes activation. A cDNA for one of the Ly-6 proteins was isolated recently and studies with this cDNA confirm that Ly-6 is a complex multigene family. We propose to use the murine cDNA to isolate and characterize a human homologue of the murine Ly-6 system. The existence of human sequences homologous to Ly-6 will be determined by probing Southern blots of human genomic DNA with the murine Ly-6 cDNA. Cells expressing mRNA homologous to Ly-6 will be identified by probing Northern blots with the Ly-6 cDNA. cDNA libraries from cells expressing Ly-6 related messages will be screened with the Ly-6 probe and homologous clones will be isolated. These human cDNA's will be characterized by restriction analysis and will be sequenced. Peptides will be synthesized based on the deduced amino acid sequences and will be used to generate specific antibodies. Full length cDNA's will be expressed in expression vectors and the isolated proteins will be used for structural studies and for the generation of specific antibodies. These cDNA's and antibodies will be utilized for studying the structure of the human Ly-6 system and the role it plays in cellular activation. The major long-term objective of this work is to identify and characterize molecules involved in the process of transducing extracellular messages and cellular activation. It has become clear recently that adherent function or control of cellular activation molecules may be an etiology for some or many human malignancies. Moreover, activated lymphocytes are an important new modality in the treatment of some human malignancies. Elucidating the human Ly-6 system should further our understanding of cancer and aid in its treatment.